1.3.5- Triazines nitriles, trimerization

Another example of the remarkable reactivity of Mg actuated by our procedure is its reaction with nitriles. In this respect, the Mg resembles an alkali metal more than an alkaline earth. Benzonitrile reacts with Mg overnight, in refluxing DME, to give 2,4,6-triphenyl-l,3,5-triazine and 2,4,5-triphenylimidazole in 26 and 27% yield, respectively, based on magnesium. Jhe imidazole was shown to arise, at least in part, from the action of Mg on the triazine. The trimerization of aromatic nitriles to give symmetrical triazines is not unknown, but generally the reactions are... 

Triazines can be obtained either by condensation methods using the fluorinated anhydride (89IZV928) or by trimerization of nitriles, e.g., per-... 

A slightly related reaction involves nitriles, which can be trimerized with various acids, bases, or other catalysts to give triazines (see OS III, 71). HCl is most often used. Most nitriles with an a hydrogen do not give the reaction. 

Trimerization of imidates is a valuable route to 1,3,5-triazines. Imidates can be considered as activated nitriles and cyclotrimerize more readily. Most symmetrical 2,4,6-trialkyl-1,3,5-triazines are easily formed, although large alkyl substituents may give rise to steric hindrance (61JOC2778). Symmetrical isocyanurates (525) are readily available from isocyanates, RNCO catalysts include tertiary amines, phosphines and sodium methoxide. Aldehydes RCHO and ammonia give hexahydro-1,3,5-triazines (526), known as aldehyde ammonias (73JOC3288). 

Probably the cyclotrimerization of nitriles is the best known route to 1,3,5-triazines. The reaction has the obvious limitation that it is of value for preparing the symmetrical derivatives only. Nevertheless, many important triazines, such as cyanuric chloride, are made in this way. There are a number of other cyclotrimerization reactions which are also useful, in particular the trimerization of imidates. An easy route to 1,3,5-triazine from ammonium acetate has been developed. 

The preparation of 1,3,5-triazine 1,3,5-trioxides by trimerization of a nitrile oxide was reported (09CB803) however, the structure of the product has been reassigned as a polymer (65LA(687)191>. 

In this context it is interesting to note that benzonitrile, Ph—C=N, trimerizes to a triazine on a Raney nickel surface. It was assumed that Jt-bonded nitriles were involved in the reaction mechanism.10 This reaction resembles the well-known template synthesis of phthalocyanine complexes from phthalodinitrile. Formation of linear polymers [—C(R)—N—] occurs on heating aryl or alkyl cyanides with metal halides.11... 

Aromatic nitriles are trimerized to symmetric triazine derivatives (c). 

Swamer et a/.246 described the formation of l,2-dihydro-2,4,6-triphenyl-1,3,5-triazine (154b) (yield 14%) from benzonitrile in the presence of sodium hydride and proposed a detailed mechanism (Scheme 8), which is, presumably, valid for all trimerizations of nitriles in the presence of organometallic reagents.243-246... 

Under high pressure, aromatic and heterocyclic nitriles can be trimerized to the 2,4,6-triaryl-1,3,5-triazines 141 176,177 the formation of dipolar intermediates as active species is assumed. The trimerization of benzonitrile in the presence of an alcohol under 2000-10000 atm at 100-120 °C involves the formation of benzimido esters as intermediates. In general, the formation of the trimer is favored with increasing pressure. On the other hand, long-chain or branched alcohols suppress the trimerization. Polar solvents increase the yield of trimer, and while acids can suppress the reaction, bases have little effect. 

Aromatic nitriles can be thermally selectively polymerized in pyrrolidin-2-one at temperatures above 200 C. Between 200 and 350 °C trimerization to 2,4,6-triaryl-l,3,5-triazines occurs, while at temperatures above 300 °C imidization occurs resulting in nonmelting, linear polyaryl-carbimine. Mixtures of trimers and polymeric imines are separable by sublimation or extraction with aromatic hydrocarbons.180 Since aryltriazines and polymeric aryltriazines have various industrial applications, several catalytic systems have been developed for the trimerization of aromatic nitriles and dinitriles, e.g. metal chlorides,181 iron(II) or iron(lll) cyanide,182 cop-per(II) carbonate,183 and molten zinc(II) chloride.184... 

The trimerization of two or three different nitriles theoretically yields four or ten different substituted triazines, respectively. Well-known and of most interest is the reaction between two different cyano-containing compounds (see also Houben-Weyl, Vol. E4, p 915ff, p 1386 Vol. E5, p 1313 ff Vol. E4, p 1220 ff). 

Imido esters, like imidoyl halides, can be considered as activated nitriles which are formed during alcohol-catalyzed trimerization reactions of nitriles, but they cyclotrimerize even more easily to the 1,3,5-triazines. The reaction can be catalyzed by an additional acid276 278,481 or carried out under high pressure.280... 

Trimerization of nitriles, isocyanates, isothiocyanates, imidates, and carbodiimides all lead to symmetrical 2,4,6-trisubstituted 1,3,5-triazines (see Section 6.12.9.5). The use of lanthanide trifluoromethanesulfonate and ammonia as cocatalysts is claimed as a big improvement. The trisaminal of 2,4,6-triformyl-l,3,5-triazine is also useful for further derivatization to unusual structures (see Section 6.12.7.1). Treatment of a 1 1 pyridine/conc. ammonia solution of an aromatic aldehyde with excess Fremy s salt is another development. Separation of the amide coproduct was claimed to be easy. The synthesis fails with aliphatic aldehydes (see Section 6.12.9.5.4). Aminolysis of 2,4,6-triaryl-1,3,5-oxadiazinium salts gives symmetrical 1,3,5-triazines but the reactions are limited in that electron-withdrawing groups in the aromatic rings lead to instability and difficulty in separation of products (see Section 6.12.10.4). 

Nitriles can also trimerize they yield triazines or aminopyrimidines according to the nature of the nitrile (cf. p. 205). 

When, for instance, acetonitrile56 is heated with an equimolar amount of dry potassium methoxide at 140° for 5 h, it affords 70% of 4-amino-2,6-dimethylpyrimidine ( cyano-methine ), but 85% of 2,4,6-tris(dichloromethyl)-s-triazine is obtained from dichloroaceto-nitrile in the presence of aluminum chloride and hydrogen chloride at room temperature.57 Benzonitrile trimerizes in an acid catalysed reaction, most simply when its solution in chloro-sulfonic acid is kept at 0° for 1-2 days, giving 2,4,6-triphenyl-s-triazine (cyaphenin),58 but 85% of l,2-dihydro-2,2,4,6-tetraphenyl-s-triazine is formed under the influence of a sodium suspension.59... 

Trimerization of aromatic nitriles requires harsh reaction conditions, high temperatures, long reaction times, and pressure. In order to obtain the desired 1,3,5-triazines under milder reaction conditions, de la Hoz e( al. have performed the cyclotrimerization of cyanopyrazole 250 in the absence of solvent using yttrium trifluoromethanesul-fonate as catalyst (Equation 32). Cyclotrimerization of pyrazolylcarbonitriles 250 produces pyrazolyl-substituted... 

Fluorinated nitrile compounds can be trimerized into fluorinated j-triazines in high yields. When Z-C3FSOCF2-CF(CF3)0CF2CF2CN 252 was treated with catalytic amounts of Ag20 at 120-140 °C neat for 10 h, the corresponding r-triazine 253 was formed in 80% isolated yield (Equation 33) <2003JOC4410>. 

Aromatic nitriles may be trimerized at moderate temperature and pressure with p-toluenesulfonic acid as catalyst. Studies were conducted to establish the effect of the reaction temperature, pressure, time, and catalyst concentration on yield of the trimerized product. Trimerization studies were also conducted to establish the effect of substituting electron donating or withdrawing groups on benzonitrile. Preliminary results of using the catalytic trimerization approach to prepare s-triazine cross-linked polyimide/graphite fiber composites are presented. 

Catalytic trimerization of p-cyanophthalanil with 5 mole percent p-toluenesulfonic acid at 250-300°C and M-.97 to 5.52 MN/m (720-800 psi) for 90 hours gave a 979 yield product, with a m.p. >3h0°C. The infrared spectrum showed the disappearance of the nitrile band at 22W cm and the broadening of the s-triazine bands at 1520 and 1380 cm ... 

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